Clinical studies have shown that, following a trigeminal tractotomy between subnuclei interpolaris and caudalis, tooth pulp stimuli continue to evoke intense pain, despite the prevailing concept that pain transmission from the head is processed exclusively in subnucleus caudalis. Neuroanatomical studies indicate that dental pulp axons terminate in all three subnuclei of the spinal trigeminal complex. It is a discrete system, amenable to manipulation, which may represent a valuable model for the examination of pain modulation in the trigeminal system. However, little is presently known about the precise spatial arrangement of descending serotoninergic (5-HT) and enkephalinergic (ENK) modulation of pain transmission between pulpal synapses and post-synaptic cells in subnuclei interpolaris and oralis. Therefore, the central theme of this proposal will be to label primary afferent terminals from the cat's dental pulp, using either anterograde transport of WGA-HRP or transganglionic degeneration, together with retrograde transport of HRP to trigemino-thalamic relay cells following an injection of the ventrobasal thalamus in a site in which maximal evoked potentials are elicited with pulpal stimulation. Immunocytochemistry, employing the avidin-biotin method and a double-labelling Protein A Gold ultrastructural technique, will then be used to quantitatively define the spatial arrangement and appositional relations of ENK and 5-HT modulatory synapses on labelled pulpal terminals and post-synaptic cells, including relay cells. This type of study will provide a basis for further physiological and structural analyses of the transmission and modulation of oral pain.